The Program in Gene Regulation and Functional Genomics (GRFGP) is derived from the former Molecular Oncology Program (MOP) which was renamed to reflect a more sharpened focus. The reorganization reflects the profound developments that have occurred in the molecular genetics of cancer, as well as in the broader field of genomics, since the last competitive renewal of this grant. Under the joint leadership of Dr. Jeffrey Sklar and Dr. Sherman Weissman (former co-Leader of MOP), the GRFGP is designed to promote (1) research into the mechanisms and effects of gene expression relevant to the neoplastic phenotype, and (2) the investigation of cancer-associated broad-based structural and functional features of the human genome. These two aspects of the GRFGP cover the study of individual genes that contribute to the development and progression of cancer as well as the analysis of genome-wide gene expression, chromatin structure, and regulatory factors that characterize or control the neoplastic state. Furthermore, the goals of the research encompassed by this program include the development of methods to better elucidate and analyze the changes in genes, gene expression, and DNA related to cancer. Finally, this program is interested in both the biologic processes underlying cancer and the application of information about those processes to the improved prevention, diagnosis, and treatment of cancer. By focusing predominantly on the molecular analysis of sporadic cancers, the GRFGP complements the activities of the Cancer Genetics Program, which is charged with the identification and analysis of genes responsible for hereditary predisposition to cancer. The two Programs engage in significant collaborations, particularly in the area of technology development. The goals of the GRFGP are accomplished through joint sponsorship of the Molecular Virology and Oncology group meetings, major participation in the Stem Cell weekly group meetings, organization of the weekly Genetics Seminar series, institution of Pilot Grant program to stimulate programmatically-oriented research in cancer, as well as by facilitating collaboration between members within the program and other Cancer Center programs. The GRFGP consists of 20 independent but interactive members belonging to eight departments of the Medical School or University. Total peer-reviewed funding support of this group is approximately $4.7 million direct costs annually ($7.5 million total costs), of which just under $1 million direct costs ($1.4 total costs) come from NCI. Total direct funding is $4,79 million ($7.65 million total costs). During the previous grant period, members of this program published 208 cancer-related papers, of which 5.3% were intraprogrammatic and 15.9% inter-programmatic.